Characteristics of TORAY FILTRYZER NF seriesThe membrane having the property of protein adsorption and suppress-

ing structural change of adsorbed proteins

changed by adsorption on membrane (Fig.1 a).In TORAY FILTRYZERTM NF (NF), we aimed at suppressing platelet adhesion on membrane surface by preventing proteins adsorbed on membrane from structural chang-es (Fig.1 b).

Design concept of a new PMMA membranePMMA has an adsorption property of several kinds of proteins. As the one of the reasons for the occurrence of coagulation during hemodialysis, it is considered that platelets are activated by adhesion on membrane sur-face because of recognizing protein structure which was

Structural change of adsorbed proteinsStructural change of albumin adsorbed on membrane was analyzed by using “Attenuated total reflection Fou-rier transform infrared spectroscopy (ATR-FTIR)”. Peak of amide bond of albumin adsorbed on NF membrane was closer to that of native albumin than that on conven-tional PMMA membrane (Fig.2).

Improvement of anti-thrombogenecityPlatelet adhesion on the NF membrane surface was lower than the conventional PMMA membrane (Fig.3). The amounts of fibrinogen adsorbed on the NF mem-brane were lower than the conventional PMMA mem-brane (Fig.4).

Relative amount of fibrinogen adsorption (%)

The PMMA-specific adsorption propertyIt is confirmed that platelet adhesion is suppressed in NF while adsorption performance in NF is almost equal to conventional PMMA (Fig. 7, 8).

Blood side

β2MG

Albumin

Coagulation protein(Fibrinogen)

Platelet

Adhesion

Structural change

Structural change

ConventionalPMMA

membrane

Dialysate side

Structurally-changed proteins

Blood side

β2MG

Albumin

Coagulation protein(Fibrinogen)

Platelet

No adhesion

PMMA NFmembrane

Dialysate side

Native structural proteins

Fig.1 Schema of the protein adsorption mechanism on the PMMA membrane1)

Ab

sorb

ance

1560 1550 1540 1530Wave number (cm-1)

Native albumin

Albumin adsorbed to NF membraneAlbumin adsorbedto conventional PMMA membrane

Fig.2 ATR-FTIR spectra of albumin adsorbed on the NF and conven-tional PMMA membranes, and native human serum albumin1)

(Data were obtained from in vitro investigation using human albumin solution and hollow fiber sliced in half lengthwise.)

1) Oshihara W et al., Contrib Nephrol. 2017:189:230-236.2) Takahashi H et al., Kidney and Dialysis (suppl.) High Performance Membrane ’13

2013:75:230-236.3) Sugaya H et al., Kidney and Dialysis (suppl.) High Performance Membrane ’06

2006:61:19-23.

Suppression of fibrinogen adsorption on membrane

Suppression of platelet adhesion on membrane

Fig.3 Platelet adsorption on membrane surface in vitro2)

(SEM image obtained from in vitro investigation using human blood.)

Conventional PMMA membrane

NF membrane

0 50 100

Fig.4 Adsorption amounts of fibrinogen2) #)

* The amount of conventional PMMA membrane is set as 100%

Protein adsorption

(kD)

205

116

97

66

55

45

30

21

14

Fig.7 Electrophoretic patterns of proteins adsorbed by membrane2) #)

Marker PS Conventional NF membrane membrane

PS Conventional NF membrane membrane

PMMA PMMA

Fig.8 Adsorption amounts of β2-microglobulin2) #)

* The amount of PS is set as 100%

Rel

ativ

e am

ou

nt o

f β

2-M

G a

dso

rpti

on

(%)

800

600

400

200

100

0

Conventional PMMA membrane New PMMA membrane (NF)

a b

PMMA membranes have a homogeneous structure, in which pores on both blood and dialysate surfaces are almost similar in size. The whole PMMA membrane acts as both a separating layer and an adsorption site for

solutes (Fig.5). PMMA membranes have adsorption prop-erties and adsorb about 8 times the amount of proteins adsorbed by polysulfone (PS) (Fig.6, in vitro study).

Unique membrane structure and protein adsorption property

Fig.6: Comparison of the amounts of proteins adsorbed by PMMA and polysulfone3).

Fig.5: Cross-sectional image of PMMA and polysulfone.

Images were obtained via electron microscopy.MW: molecular weight, PBUTs: protein-bound uremic toxins

Rel

ativ

e ad

sorb

ed a

mo

unt

* (%

)

* The amount of PS is set as 100%

Separating layer Separating

layer

4) Masakane I et al., Renal Replacement Therapy 2017:3:325) Uchiumi N et al., Renal Replacement Therapy 2018:4:32#: Results were obtained from in vitro investigation using human plasma

Low MW proteins (ex. β2-microglobulin etc.)

Printed in Japan 2006 G1

Manufacturer:

Toray Industries, Inc.1-1, Nihonbashi-Muromachi 2-chome, Chuo-ku, Tokyo 103-8666, JAPAN

Exporter:

Toray Medical Co., Ltd.4-1, Nihonbashi-Honcho 2-chome, Chuo-ku, Tokyo 103-0023, JAPAN

Toray International Italy S.r.l.Via Mecenate 86, 20138 Milan, ITALY

0123

Sieving Coefficient of Albumin (Target)

Expected effect of albumin leakage controlled dialyzer NF-U series.Characteristics of PMMA Membrane

1) Suppression of platelet activation.

2) Improvement of dialysis pruritus and unidentified side-effects4)5).

3) Improvement of nutritional condition of patients5).

• Excellent Biocompatibility1)

• Protein adsorption properties and it can remove large molecular weight proteins.

• Good removal balance of small uremic toxins and high-molecular weight substances.

Expected characteristics of Filtryzer NF SeriesBy modifying the membrane surface that suppresses the structural change of the adsorbed protein, we succeeded in suppressing platelet adhesion and further improving biocompatibility.

Various clinical reports on NF Series

NF-U has a feature of minimized albumin leakage, and it also allows to use comfortably for patients who are

concerned about malnutrition.

NF-U NF-H

0.003

0.009

Specifications NF-U Series

Type NF-1.3U NF-1.6U NF-1.8U NF-2.1U

Fibers Effective surface area (m2) 1.3 1.6 1.8 2.1

Effectie length (mm) 195

Inside diameter (μm) 200

Membrane thickness (μm) 30

Blood volume (mL) 83 103 118 135

Clearance (mL/min)* Urea 233 246 254 260

Creatinine 200 217 225 231

Phosphate 182 198 208 217

Vitamin B12 110 128 140 149

Inulin 62 72 77 85

UFR in vitro (mL/hr/mmHg) ** 32 38 45 48

* Clearance are typical data with aqueous solution. (QB: 300 mL, QD: 500±10 mL/min, QF: 10±2 mL/min, Temp.: 37±1 °C)** UFRs are typical data with bovine blood. (Ht: 32±3 %, TP: 6.0±0.5 g/dL, QB: 300 mL/min, TMP: 50 mmHg, Temp.: 37±1 °C)